Altered peptide ligand modulation of experimental allergic encephalomyelitis

Immune responses within the CNS

Laura Santambrogio, Marjorie B. Lees, Raymond A. Sobel

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

An altered peptide ligand (analog) of the encephalitogenic epitope of proteolipid protein residues 139-151 (p139-151) in which residues 144 and 147 are substituted with leucine and arginine, respectively (LR), protects from clinical but not histological experimental allergic encephalomyelitis (EAE). To understand in situ events associated with this protection, T cells from brains of mice immunized with either native p139-151, the analog LR or a combination of the two were isolated and characterized. High proportions of cells from co-immunized mice (38%) and LR-immunized mice (58%) reacted to both p139-151 and LR, whereas fewer cells from p139-151 immunized mice (7%) were cross-reactive. T cell clones derived from brains of LR- and co- immunized mice were also cross-reactive in vitro. By reverse transcriptase- based polymerase chain reaction, higher levels of TGF-β mRNA, and lower levels of TNF-α and IFN-γ mRNA were found in the central nervous system (CNS) tissue of LR and co-immunized mice. Immunohistochemistry demonstrated greater TGF-β immunoreactivity in CNS inflammatory loci in co-immunized and LR-immunized mice. There were no significant differences in CD4+ or CD8+ cell infiltrates among the groups and differences in other cytokines were not identified by immunocytochemistry. Protection from clinical EAE in LR and co- immunized mice was partially abolished by anti-TGF-β antibody treatment. Thus, protection from clinical disease following immunization with the analog LR is associated with infiltration into the CNS of a T cell population that could potentially recognize the native PLP peptide and with enhanced TGF-β production by cells within CNS inflammatory foci.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalJournal of Neuroimmunology
Volume81
Issue number1-2
DOIs
StatePublished - Jan 1998
Externally publishedYes

Fingerprint

Autoimmune Experimental Encephalomyelitis
Central Nervous System
Ligands
Peptides
T-Lymphocytes
Immunohistochemistry
Nerve Tissue
Messenger RNA
Proteins
Brain
Reverse Transcriptase Polymerase Chain Reaction
Leucine
Arginine
Epitopes
Anti-Idiotypic Antibodies
Immunization
Clone Cells
Cytokines

Keywords

  • Autoimmunity
  • Cytokines
  • EAE
  • Neuroimmunology
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Altered peptide ligand modulation of experimental allergic encephalomyelitis : Immune responses within the CNS. / Santambrogio, Laura; Lees, Marjorie B.; Sobel, Raymond A.

In: Journal of Neuroimmunology, Vol. 81, No. 1-2, 01.1998, p. 1-13.

Research output: Contribution to journalArticle

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abstract = "An altered peptide ligand (analog) of the encephalitogenic epitope of proteolipid protein residues 139-151 (p139-151) in which residues 144 and 147 are substituted with leucine and arginine, respectively (LR), protects from clinical but not histological experimental allergic encephalomyelitis (EAE). To understand in situ events associated with this protection, T cells from brains of mice immunized with either native p139-151, the analog LR or a combination of the two were isolated and characterized. High proportions of cells from co-immunized mice (38{\%}) and LR-immunized mice (58{\%}) reacted to both p139-151 and LR, whereas fewer cells from p139-151 immunized mice (7{\%}) were cross-reactive. T cell clones derived from brains of LR- and co- immunized mice were also cross-reactive in vitro. By reverse transcriptase- based polymerase chain reaction, higher levels of TGF-β mRNA, and lower levels of TNF-α and IFN-γ mRNA were found in the central nervous system (CNS) tissue of LR and co-immunized mice. Immunohistochemistry demonstrated greater TGF-β immunoreactivity in CNS inflammatory loci in co-immunized and LR-immunized mice. There were no significant differences in CD4+ or CD8+ cell infiltrates among the groups and differences in other cytokines were not identified by immunocytochemistry. Protection from clinical EAE in LR and co- immunized mice was partially abolished by anti-TGF-β antibody treatment. Thus, protection from clinical disease following immunization with the analog LR is associated with infiltration into the CNS of a T cell population that could potentially recognize the native PLP peptide and with enhanced TGF-β production by cells within CNS inflammatory foci.",
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